The long-range objectives of the FCRR Multidisciplinary Learning Disabilities Center are to (1) compare alternative approaches for defining, classifying, and preventing learning disabilities in decoding, reading comprehension, spelling, and written composition;(2) determine how prevalent learning disabilities are among struggling readers;(3) determine how learning disabilities are related to learning abilities;(4) determine how learning disabilities in one domain are related to learning disabilities in other domains;(5) identify key environmental liabilities and assets that affect the occurrence and expression of learning disabilities;and (6) identify key genetic liabilities and assets, and genetic-environmental correlations that affect the occurrence and expression of learning disabilities. These objectives will be pursued in large-scale, developmental, multivariate contexts that distinguish and address both theoretical and practical issues, and that explicitly address level of severity. Project I addresses alternative approaches to classification and prevention that include new measures of emergent literacy and response to instruction in a large-scale study of 1,500 preschool-age children. Project II addresses alternative approaches to classification, the role of effective instruction in preventing or minimizing the expression of learning disabilities, and a fundamental assumption of response to instruction models in two large-scale study of 1,420 elementary-school children. Project III addresses etiology, identification, and classification in a state-wide sample of over 100,000 children in Reading First schools, and in a large-scale, twin-based quantitative genetic study of 9,000 pairs of twins. Project IV addresses the molecular genetics and behavioral characteristics of profound reading impairment in a family study of 500 probands. Project V addresses underlying dimensions of performance in vocabulary and fluency, and tests alternative models of the development of reading and writing in a four-year longitudinal study of 300 children from first through fourth grade. The relevance of this application to public health is its potential for improving prevention, early identification, and effective remediation of learning disabilities.